Respiratory epithelial expression of integrin alphaVbeta6 in chronic progressive allograft rejection.

Abstract

BACKGROUND: Obliterative bronchiolitis (OB) is the major cause of morbidity and mortality after lung transplantation. One initiating event in the development of obliteration of the airway lumen is epithelial injury. In our model of chronic rejection, initial ischemic injury and denudation of the epithelium occurs in the isografts, with eventual re-epithelialization and partial patency of the airway lumen. In contrast, allografts do not recover epithelium, and the airway lumen becomes obliterated. We hypothesized that because integrin alphaVbeta6 is expressed in healing epithelium, integrin alphaVbeta6 expression would be greatly increased in isografts, but not in allografts. METHODS: Using a rat tracheal allograft rejection model as a source of 4- to 5-microm tissue sections, we compared integrin staining in allografts vs isografts from animals at post-transplant Days 7, 14, 28, and 60. We analyzed the sections using immunohistochemistry after incubation with a specific monoclonal antibody E7P6 against integrin alphaVbeta6. Negative control slides were processed identically, except that primary antibody was omitted. RESULTS: The sections from healing, re-epithelializing isografts showed intense staining when using the antibody recognizing integrin alphaVbeta6, compared with the allografts studied. Days 7 and 14 isografts had increased epithelial expression of alphaVbeta6. As the isograft epithelium recovered, the intensity diminished at Days 28 and 60. In allografts, at Days 7 to 60, we detected only a comparatively low-level of expression in injured epithelium. CONCLUSIONS: Integrin alphaVbeta6 is readily detectable in healing isografts. Integrin alphaVbeta6 may be crucial in maintaining a viable epithelial cell layer, which is related to slowed progression of airway obliteration in OB.